Hemangiosarcoma Research for Rottweilers: Q&A with Dr. Modiano

The majority of Rottweiler guardians will agree that there is no canine cancer more terrifying than hemangiosarcoma (HSA). This type of cancer is not only hard to detect but also presents significant challenges in terms of treatment. HSA has the potential to deliver a devastating blow when a tumour ruptures, leading to internal bleeding and ultimately death. 

The University of Minnesota has made significant strides in combating the devastating cancer known as hemangiosarcoma (HSA) through promising research. This groundbreaking work has been ongoing for over twenty years, resulting in a combination of diagnostic and treatment strategy that offers a unique approach. The Shine On Suspicion (SOS) blood test plays a crucial role in this strategy by identifying specific characteristics of rare cells in the blood associated with this insidious cancer. This early detection allows for the potential of initiating treatment at an earlier stage. Additionally, dogs identified as high-risk for HSA based on the SOS test results may have the opportunity to receive a novel targeted toxin therapy called eBAT, which has been developed at the University of Minnesota. This innovative treatment has the potential to extend the lives of affected dogs.

Bear in mind that although the SOS blood test and eBAT are gaining favour in clinical trials, both are months to years from being widely available in veterinary clinics. “We hope to move the SOS blood test to the real world soon, so dogs can be tested through their veterinarian,” says Jaime F. Modiano, VMD, PhD, the Perlman Endowed Chair in animal oncology at the University of Minnesota. “eBAT will remain experimental until it is approved by the Food and Drug Administration as a treatment modality, and then additional work will be needed before it can be used for preventive purposes.”

The complexity of HSA is notable as reflected in the diversity of its manifestation in individual dogs. More than 50 percent of affected dogs die within four to six months, almost 90 percent within a year. A tumour ruptures causing acute, severe blood loss, collapse, shock, and sudden death in many cases. “This cancer has high metastatic propensity and is extremely drug-resistant, making it one of the most aggressive cancers seen in dogs,” Dr. Modiano says.

Although much is unknown about HSA, characteristics of the cancer define its idiosyncratic nature. “One of the most challenging things about HSA is that it grows silently and initially without clinical signs,” says Dr. Modiano. “The diagnosis is typically made when the cancer is in the advanced stages and hard to treat.”

More than 50,000 companion dogs in the U.S. are believed to develop HSA each year, estimates the University of Minnesota research team. Naturally, people who have lost dogs to this cancer seek ways to prevent it from occurring in other dogs. “There is no known effective preventive,” he says. “Altering lifestyle behaviours, reducing environmental concerns, or feeding special diets or supplements have no impact on the development of this cancer.”

HSA originates from bone marrow cells that play a role in the formation of new blood vessels throughout the body. This characteristic enables tumour cells to access various tissues. The spleen is the most common site for tumour development, followed by the heart, skin, and liver. HSA cells stimulate the creation of abnormal blood vessels where blood tends to accumulate and clot. Over time, these clots obstruct the vessels, preventing fresh blood and essential nutrients from reaching the tumour environment. Consequently, the lack of nourishment leads to cell death. As a result, the tumour experiences ruptures, causing blood to escape into different areas such as the abdomen, heart sac, chest, or subcutaneous tissue, depending on the tumour's location.

The objective of treatment is to impede or delay the progression of the disease, with a crucial focus on preventing life-threatening bleeding episodes. The current standard of care involves surgical removal of the tumour mass, followed by chemotherapy. 

The combination of the SOS blood test and eBAT treatment, pioneered at the University of Minnesota, represents a significant advancement in the fight against HSA. The SOS blood test was developed using over 40 characteristics of rare cells found in the blood of dogs diagnosed with HSA. By utilizing artificial intelligence, this test can analyze a dog's susceptibility to developing HSA based on these specific parameters.

eBAT, which stands for EGF-bispecific angiotoxin, is a treatment method that administers a potent bacterial toxin payload to tumour cells. It achieves this by targeting two proteins, namely epidermal growth factor receptor (EGFR) and urokinase-type plasminogen activator receptor (uPAR), which are present on the cell surfaces of HSA tumours. The identification of these proteins being expressed simultaneously led to the hypothesis that a targeted therapy attacking both proteins simultaneously could prove effective in treating HSA tumours.

“After eBAT is injected into a vein, it enters tumours where it specifically kills malignant cancer cells that display EGFR and uPAR on their surface,” Dr. Modiano says. “Another unique property of eBAT is that it kills inflammatory cells and blood vessels in and near tumours, making the environment inhospitable for the cancer cells. Importantly, eBAT does not cause any severe side effects.”

The ongoing study aims to generate valuable insights regarding the effectiveness of the SOS blood test in predicting the likelihood of dogs developing HSA. It seeks to determine the timeframe before tumours develop in dogs identified as high risk, as well as whether dogs categorized as low or medium risk eventually develop tumours. Additionally, the study aims to assess whether the treatment of high-risk dogs with eBAT can potentially alter their risk status to low or medium.

“The concept is that the properties of the SOS blood test and eBAT set this combination apart. They not only predict if a dog is at high risk or perhaps has an incipient HSA, but also provide a way to reverse that and prevent the tumour from ever forming,” says Dr. Modiano.

While the SOS blood test and eBAT await approval for veterinary clinical use, the best advice for the owner of a dog suspected of having cancer is to see a specialist. “We recommend consulting and following the advice of a specialist,” Dr. Modiano says. “It is important to conform to best medical practices and not give in to practices that give false hope. Talk to your dog’s health care team to understand the results of tests and options available.”   

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